1. Field of the Invention
The embodiments of the present invention relate generally to methods and devices for nucleic acid sequencing and the electronic detection of nucleic acid sequencing reactions.
2. Background Information
Genetic information in living organisms is contained in the form of very long nucleic acid molecules such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Naturally occurring DNA and RNA molecules are typically composed of repeating chemical building blocks called nucleotides which are in turn made up of a sugar (deoxyribose or ribose, respectively), phosphoric acid, and one of four bases, adenine (A), cytosine (C), guanine (G), and thymine (T) or uracil (U). The human genome, for example, contains approximately three billion nucleotides of DNA sequence and an estimated 20,000 to 25,000 genes. DNA sequence information can be used to determine multiple characteristics of an individual as well as the presence of and or susceptibility to many common diseases, such as cancer, cystic fibrosis, coronary heart disease, diabetes, and sickle cell anemia. Determination of the entire three billion nucleotide sequence of the human genome has provided a foundation for identifying the genetic basis of such diseases. A determination of the sequence of the human genome required weeks or months to accomplish. The need for nucleic acid sequence information also exists in personalized medicine, research, environmental protection, food safety, biodefense, and clinical applications, such as for example, pathogen detection (the detection of the presence or absence of pathogens or their genetic variants).
Thus, because DNA sequencing is an important technology for applications in bioscience, such as, for example, the analysis of genetic information content for an organism, tools that allow for faster and or more reliable sequence determination provide significant value. Applications such as, for example, population-based biodiversity projects, disease detection and diagnosis, prediction of effectiveness of drugs (personalized medicine), biomarker discovery through disease-genotype association, genotyping using single-nucleotide polymorphisms, and drug development through gene expression profiling studies stimulate the need for simple and robust methods for sequencing long or short lengths of nucleic acids (such as, for example, those containing 1-20 bases). Sequencing methods that provide increased accuracy and or robustness, decreased need for sample preparation, and or high throughput are valuable analytical and biomedical tools.